Quinoline derivatives and a process



Patented July 24, I934 UNITED STATES PATENT OFFICE No Drawing;

Application November 12, 1930,

Serial-No. 485,295. In Germany December 6,

derivatives anda P Ocess of preparing them, more particularly to compounds of the following generalformulaz 7 N OIf OE-R wherein X stands for hydrogenor alkoxy containing no more than 2 carbon atoms and R M stands for alkyl or aralkenyl. 1 H a g t I have found that i-aminoquinolines. containing in 2-positiori an unsaturated side chain consisting of at least 3 carbon atoms, and which may contain any substituent or substituents, are dis- 2" tinguished by a bactericidal action which surpasses that of the 2-styryl-4-amino-quino1ines obtainable according to German specification 440,008.

The new compounds can be obtained by substituting in any order of succession in 2-methyl i-halogen-quinoline, or in a nuclear substitution product thereof, an amino-group for halogen and converting the .2 -methyl-group with alkyl-, alkylene-, aralkyl, or aralkylene-aldehydes into an unsaturated radical.

The procedure may for instance be as follows:

a 2-methy1-4-halogen-quino1ine is condensed with an alkyl-, alky1ene-, ara1kyl-, or aralkylenealdehyde and the t4- halogen-quinoline formed, containing in 2-position an unsaturated chain consisting of l at least 3 CfllbOIlfltOlfiS, is heated with ammonia or a primarymor secondary amine;

or a 1Z-methyIAQhalOQen-quinoIine "ls transformed by heating with ammonia or a primary or secondary amine into a z-niethyl-i-aminoquinoline and this is condensed with an alkyl-, alkylene-, aralkylor aralkylene aldehyde.

The following examples serve to illustrate the invention, but they are not intended to limit it thereto; the parts are by weight, unless otherwise stated 7 c 1. 221.5 parts of fi-ethoxy-4-chloro 2?metbylquinoline, 114 par s of oemnthic aldehyde (heptanal) and 1 part of zinc chloride' are heated toy a I solaimsftcrz so-iss) The present invention relates to"quinoline gether for 4 hours at a temperature of 120 C.-- 130 C. The reaction following equation" takes place according to the The water split oil is distilled in a vacuum. The resinous'melt. mainly consisting of fi-ethoxyrf chloro zoctenyl quinoline, is dissolved in 1000 parts of phenol. ,v Whileintroducing a current of ammonia, the solution is kept gently boiling for 2 hours. After cooling, a nearly colorless product is precipitated from the mixture by means of ether; by recrystallization from dilute alcohol, admixed double chloride of zincand ammonia is removed and, by dissolving the dried substance in a small quantity of alcohol and precipitating with ether, the 2-octeny1-4-amino-6-ethoxyquinoline hydrochloride of the following probable constitution ,t

" .HOI

V y Ni \CH=CH-(CH2): CH; obtainedin the former a colorless powder being only' sparingly soluble in water. a

192, 321,5 parts of G-ethoxy-4 chloro-2-methylquinoline, "132 parts of cinnamic aldehyde and 1 part of zinc chloride are heated together for 2 hours,while stirring; at a temperature of 125 (ii-130 C. 1500 parts by volume of doublenormal hydrochloric acid are then added u: the *viscous melt, whereby a yellow crystalline precipitate separates, which, after being filtered by suction; is washed with dilute hydrochloric acid and then withacetone and dried. The2-(delta-phenyl-- allowed to stand in the cold for severalhours, it is filtered and the solid matter is washed with v acetone and recrystallized from methyl alcohol of 66% strength for completely; purifying it; The 2 -(delta-phenylbutadienyl) 4 -amino- 6gethox yquinoline-hydrochloride of the following probable constitution NHz crystallizes in the form ,of fine yellow crystals containingwat'er of crystallization which is e1iminated by heating them in a vacummat- 150 C; It only sparingly dissolves in water. The base, separated from the aqueous solution iof the salt by addition of caustic soda solution, melts at 185 C.187 c. z

8; 20 "parts ofi 6-ethoxy-4-amino-2- methylquinoline, obtained by treating 6 ethoxy-4- chloro-2-methyl-quinoline in the presence of phenol with ammonia, 15 parts of butyraldehyde, 11 parts of acetic anhydride and 1 ,part -,of .pulverized anhydrous zinc chloride'are slowly heated, while stirring, and the mixture is kept for 1 hour in an oil bath of 130 C. The cle'ar, .'yell0wishbrown melt formed is poured into 500 parts of hot water and steam is passed through the solu-. tion until the excess ofbutyraldehyde i's'elimihated. Then'50 parts by volume of hydrochloric acid; having a specific gravityof 1.19,'are added, whereby the 2-pentenyl-4ramino fi-ethoxy-quindine-hydrochloride of the following probable cdnstitution h u t Mil tia,tempe e a reflux ppae.

ratus while introducing a current of, ammonia. lifter cooling; the solution is; precipitated with ether, i it. ;has been; allowed to, stand for;

some time the salt is filtered by suction. By dissolving in methyl alcohol and precipitating with caustic soda solution, the base is separated in the form of a viscous smeary mass; after stirring several times with water containing ammonia and decanting, the base is dissolved in dilute acetic acid and a small quantity of undissolved brown flakes is filtered by suction. On addition of hydrochloric acid to the solution, there is precipitated the hydrochloride'of 2-pentenyl 4 amino- G-ethoxy-quin'oline of the following probable constitution 7.

HgaCzO which is nearl'y insoluble in an excess of hydrochloric acid; for comp letely purifying it, it is ;,recrystallized from dilute acetone.

The salt is insoluble in dry acetone, only sparingly soluble in water, but easily soluble in acetone containing water.

Itis easily soluble in chloroform, benzene, acetic ester. It decomposes at about 237 C The .ba'se, when'precipitated from the hot, aqueous solution of the saltwith caustic soda solution, "forms a colorlesspowder melting at 110 C.

I claim:

1. The compounds of the following formula:

IIIH:

" wherein R stands for propyl, hexyl or phenylethylenyl;

-3.' The compound of the following formula IIIH:

. H =Q the hydrochloride of which is. a colorless powder, sparingly soluble in waters Theicompoun'dof the vfollowing formula oH=oH oH='oH melting at 185? C 187 0., the hydrochloride of which crystallizes'in' the form of line yellow crystals containing water of crystallization which is eliminated at150- C. in a vacuum. a 7

5. The compound of the following formula 

